Safety, Tolerability, and PK of GT0918 (Proxalutamide) in Subjects With Metastatic Castrate Prostate Cancer

The starting dose cohort in the dose escalation stage will be 50 mg GT0918 (proxalutamide) PO
once daily administered to 3 subjects in a fasted state. The next dose cohort in the dose
escalation stage will be 100 mg PO once daily administered to 6 subjects in a fasted state
with escalation to the following dose levels, each having a total of at least 6 subjects per
cohort: 200 mg, 300 mg, 400 mg, and 500 mg. Dose escalation can occur after a minimum of 3
subjects in the 50 mg dose level have completed 28 days of treatment, no DLTs have occurred
and the safety review of the cohort has been performed. Dose escalation in the remaining
cohorts can occur after a minimum of 6 subjects have completed 28 days of treatment, either
no DLTs or ≤1 subject has a DLT, and the safety review of the cohort has been performed.

During the dose escalation stage, all subjects will take GT0918 oral administration once
daily on an empty stomach (fasted state) for 28 consecutive days. The first dosing cycle will
be followed by at least a 7-day off-treatment period (for PK analysis); however, no
off-treatment period will be scheduled between subsequent treatment cycles. If individual
subjects on GT0918 show an objective response or stable disease (SD) according to Response
Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria and who is expected to benefit
from continued treatment in the opinion of the investigator, they may continue to receive
additional cycles of GT0918 in the absence of untoward or serious toxicity; however, no
subject is permitted to start a subsequent cycle after each bi-monthly disease evaluation
until it is confirmed that disease progression has not occurred. A subject without disease
progression may continue GT0918 treatment with the approval of the investigator; treatment
can continue until a subject experiences an intolerable adverse event (AE) or disease
progression, withdraws consent or until termination of the study by the sponsor. A total of 6
cycles of GT0918 is planned; however, subjects without progressive disease (PD) have the
option to continue with their assigned dose in a 6-month Extension Study. At the end of total
6 cycles of GT0918 or additional extension cycles, a post-treatment period of 4 weeks will
commence that concludes with an end-of-study visit.

The recommended Phase 2 dose (RP2D) will be based on the safety, tolerability,
pharmacodynamic, and/or anti-tumor activities, etc. of GT0918 from the dose escalation stage.

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure being
performed.

2. Subjects at least 18 years of age or older at the time of consent.

3. Histologically confirmed metastatic castrate resistant cancer (mCRPC) who progressed
after both hormonal therapy (abiraterone or enzalutamide) and chemotherapy (docetaxel,
for example); or cannot tolerate either or both of these classes of therapies.

4. Ongoing androgen deprivation therapy with a luteinizing hormone-releasing hormone
(LHRH) "super-agonist" or antagonist, or bilateral orchiectomy and serum testosterone
level < 50 ng/dL (< 0.5 ng/mL, < 1.7 nmol/L) at screening.

5. Metastatic disease documented by computed tomography (CT)/magnetic resonance imaging
(MRI) or bone scan.

6. Progressive disease despite ongoing androgen deprivation or chemotherapy. Progressive
disease is defined by 1 or more of the following criteria:

- Subjects with a rising PSA value > 2 ng/mL in at least 2 measurements, at least 1
week apart. If the confirmatory PSA value is less than the screening PSA value,
then an additional test for the rising PSA is required to document progression.

- Subjects with measurable disease, progression defined by Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1 criteria.

- Subjects with metastatic bone disease, progression defined by 2 or more new
lesions in a radionuclide bone scan.

7. ECOG performance status of 0-2 (dose escalation phase); ECOG performance status of 0-1
(expansion phase).

8. Screening blood counts of the following:

- Absolute neutrophil count ≥ 1500/μL

- Platelets ≥ 100,000/μL

- Hemoglobin > 9 g/dL

9. Screening chemistry values of the following:

- Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 2.5 × upper
limit of the normal reference range (ULN)

- Total bilirubin ≤ 2 × ULN

- Creatinine ≤ 1.5 × ULN

- Albumin > 2.8 g/dL.

10. At screening, life expectancy of at least 3 months.

11. Subjects whose partners are women of childbearing potential (WOCBP) must use an
adequate method of birth control while on study drug and at least for 3 weeks after
discontinuation of study drug.

12. Subject is willing and able to comply with all protocol required visits and
assessments.

Exclusion Criteria:

1. Subjects with life expectancy less than 3 months.

2. Discontinuation of bicalutamide or nilutamide less than 6 weeks, and other
antiandrogens less than 4 weeks, abiraterone less than 3 weeks, prior to the start of
study medication.

3. Prior chemotherapy, radiation, sipuleucel-T or other experimental immunotherapy less
than 4 weeks prior to the start of study medication.

4. Prior chemotherapies more than 2 lines (Phase II part only) .

5. Ongoing acute treatment-related toxicity associated with a previous therapy greater
than grade 1 except for grade 2 alopecia or neuropathy.

6. History of impaired adrenal gland function (eg, Addison's disease, Cushing's
syndrome).

7. Known gastrointestinal disease or condition that affects the absorption of GT0918.

8. History of congestive heart failure New York Heart Association (NYHA) class III or IV
or uncontrolled hypertension at screening.

9. History or family history of long QT syndrome.

10. History of other malignancy within the previous 3 years, except basal cell or squamous
cell carcinoma, or non-muscle invasive bladder cancer.

11. Use of systemic glucocorticoid (eg, prednisone, dexamethasone) within 14 days prior to
the start of study medication.

12. Co-administration of CYP3A4 ligands that serve as substrates or induce or inhibit the
enzyme.

13. Prior use of any herbal products known to decrease PSA levels (eg, PC-SPES or saw
palmetto) within 30 days prior to the start of study medication.

14. Major surgery within 30 days prior to the start of study medication.

15. Blood transfusion (including blood products) within 1 week of screening.

16. Serious persistent infection within 14 days prior to the start of study medication.

17. Serious concurrent medical condition including CNS disorders.

18. Previous history of difficulty swallowing capsules.

19. Known hypersensitivity to GT0918 or its excipients.

20. Any condition that, in the opinion of the investigator, would impair the subject's
ability to comply with study procedures.